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Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study.

ABSTRACT: HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-?, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).We found liver fibrosis (APRI) was 50% lower in Elites and ARTc compared to ARTuc. Higher liver fibrosis was associated with significantly low CD4+ T cell counts (P?

SUBMITTER: Desai SN

PROVIDER: S-EPMC5370796 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study.

Desai Seema N SN Dodge Jennifer L JL Landay Alan L AL Glesby Marshall J MJ Latham Patricia S PS Villacres Maria C MC French Audrey L AL Gange Stephen J SJ Greenblatt Ruth M RM Peters Marion G MG

Medicine 20160801 33

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T ...[more]

PMID: 27537569

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Project description:Abstract Background Hepatic fibrosis in individuals with HCV/HIV coinfection or HCV mono-infection may be modulated by a variety of host factors. In this study, we investigated the role of gene polymorphisms of putative genes that might influence fibrosis progression including MICA (rs2596542), interferon-stimulated gene OAS2 (rs1293762) and the pathogen recognition receptors TLR7 (rs179009) and TLR9 (rs187084). Effect on a cytokine panel was evaluated. Methods Longitudinal samples were obtained from subjects enrolled in the NCI Multicenter Hemophilia Cohort Study. Within the cohort, a subset of subjects were included based upon presence or absence of the CCR5 delta-32 mutation which was previously shown to influence the rate of fibrosis progression. Hepatic fibrosis change was determined using the serum-derived Enhanced Liver Fibrosis (ELF) Index. Four putative genes with polymorphisms that have been previously associated with the development or progression of hepatic fibrosis were evaluated using Taqman SNP genotyping assays. Cytokine assays were performed using Luminex chipsets. Samples were analyzed using Statistix 10.0 using ANOVA and least square regression models. Results 58 unique subjects were evaluated. The mean age was 38 years, and all were male. 74% were HIV infected and 97% were HCV infected (76.8% coinfection). Controlling for the effect of CCR5, only the TLR7 A -> G polymorphism was predictive of change in the ELF Index. There was no statistically significant predictive difference between genotypes in the other three polymorphisms. Subjects with the TLR7 A allele (n = 47) had an average increase in ELF of 0.79 units, while the G allele (n = 11) had an increase in ELF of 2.1 units (P = 0.008). A regression model identified TLR7 as a key factor in ELF change, as well as HCV/HIV coinfection. Interferon alfa-2 levels were highly associated (increased, P = 0.0007) with the TLR7 A -> G polymorphism, while RANTES levels were inversely associated (decreased, P = 0.0443) with it. Conclusion Of the gene polymorphisms investigated, only TLR7 (rs179009) is an independent predictor of development of hepatic fibrosis in HCV/HIV coinfected subjects. The mechanism may involve modulation of inflammatory response pathways. Disclosures All authors: No reported disclosures.

Dataset Information

Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study.

Publications

Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women's interagency HIV study.

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